We are studying the molecules and cells involved in the induction of B cell immune responses. Currently, our attention is focused on the idea that B cells require at least two signals to respond to antigen. For red blood cell bound antigens the initial signal is provided by antigen alone, and initiates division. A second signal, which can be delivered by a T cell-derived nonspecific mediator, is required later in the response and induces at least differentiation into antibody production. We are testing the theory that T cells which produce this signal in normal immune responses recognize antigen directly on the B cell surface, in association with I region encoded molecules. In our hands antigen and this nonspecific mediator are not sufficient for B cell responses to protein-bound antigens. We are testing the theory that another type of helper T cell must contribute to the early antigen signal in order for it to be effective in this case. We are also studying the properties, activity and degradation of the nonspecific mediator mentioned above.